tbuckley/cabot-search huggingface dataset:
The Population Doomsday Forecast: Lessons from Kerala
Authors: J A Black
Journal: Journal of the Royal Society of Medicine (1993)

The discussion of fertility decline in Kerala state, India, focused on fertility decline in Kerala state and the role of the UN. Key features of Kerala's success in fertility decline were the emphasis on female education and the emancipation of women, reduced infant and child mortality rates, and political support. Since 1956 when the states of Cochin and Travancore were joined, the development of education and health services was encouraged. Literacy was over 90% in Kerala compared to 62% for males and 34% for females in India in 1990. Kerala's government invested in primary and secondary education, primary health care, and family planning services. 12% of Kerala's education budget is devoted to "higher" education compared to 47% of national government expenditures. Inheritance of property was matrilineal. 85% of girls aged under 14 years stayed in school in Kerala compared to 21% nationally. The mean age of marriage is 21.9 years compared to 18.3 years nationally. The sex ratio, life expectancy, and child mortality rates were favorable to females. In 1987 the crude birth rate was 22/1000 population in Kerala and 32/1000 nationally. The infant mortality rate was 27/1000 live births in Kerala and 94/1000 nationally. Contraceptive use in Kerala was predominately female sterilization, followed by the condom. Successful features of Kerala's fertility decline are potentially transportable to African countries where women already play an important role in trade and shopkeeping. Emphasis must be simultaneously placed on primary health care and free family planning services that are easily accessible at all levels of health care. With political will, African or poor countries should be able to afford these programs. The UN and its agencies should be the unifying force promoting and supporting education, primary health care, and family planning services on a worldwide scale. However, the authority and expertise within the UN has not been sufficient to meet this challenge.
Control of Neonatal Group B Streptococcal Infection
Authors: Russell W Steele
Journal: Journal of the Royal Society of Medicine (1993)

Group B beta-haemolytic streptococcus (GBS) is the leading cause of life-threatening perinatal infection in developed countries. As immunization of women is not yet available, selective intrapartum chemoprophylaxis appears to be the best current strategy for preventing disease. All pregnant women should be screened for GBS at 26 to 28 weeks gestation. During labour, all colonized women with risk factors for invasive GBS neonatal infection should be treated with intravenous penicillin or ampicillin. Risk factors include preterm labour, premature rupture of membranes, intrapartum fever, multiple births, prolonged rupture of membranes, maternal diabetes, previous sibling with invasive GBS disease, and maternal GBS bacteriuria. The latter two categories warrant chemoprophylaxis regardless of maternal colonization status.
Single-cell analysis reveals clonally expanded tumor-associated CD57<sup>+</sup>CD8 T cells are enriched in the periphery of patients with metastatic urothelial cancer responding to PD-L1 blockade
Authors: Michael Fehlings, Leesun Kim, Xiangnan Guan, Kobe Yuen, Alireza Tafazzol, Shomyseh Sanjabi, Oliver A Zill, Deepali Rishipathak, Andrew Wallace, Alessandra Nardin, Siming Ma, Ana Milojkovic, Evan W Newell, Sanjeev Mariathasan, Mahesh Yadav
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background A growing body of evidence suggests that T-cell responses against neoantigens are critical regulators of response to immune checkpoint blockade. We previously showed that circulating neoantigen-specific CD8 T cells in patients with lung cancer responding to anti-Programmed death-ligand 1 (PD-L1) (atezolizumab) exhibit a unique phenotype with high expression of CD57, CD244, and KLRG1. Here, we extended our analysis on neoantigen-specific CD8 T cells to patients with metastatic urothelial cancer (mUC) and further profiled total CD8 T cells to identify blood-based predictive biomarkers of response to atezolizumab. Methods We identified tumor neoantigens from 20 patients with mUC and profiled their peripheral CD8 T cells using highly multiplexed combinatorial tetramer staining. Another set of patients with mUC treated with atezolizumab (n=30) or chemotherapy (n=40) were selected to profile peripheral CD8 T cells by mass cytometry. Using single-cell transcriptional analysis (single-cell RNA sequencing (scRNA-seq)), together with CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) and paired T-cell receptor (TCR) sequencing, we further characterized peripheral CD8 T cells in a subset of patients (n=16). Results High frequency of CD57 was observed in neoantigen-specific CD8 T cells in patients with mUC responding to atezolizumab. Extending these findings to bulk CD8 T cells, we found higher frequency of CD57 expressing CD8 T cells before treatment in patients responding to atezolizumab (n=20, p&lt;0.01) but not to chemotherapy. These findings were corroborated in a validation cohort (n=30, p&lt;0.01) and notably were independent of known biomarkers of response. scRNA-seq analysis identified a clonally expanded cluster enriched within CD57 + CD8 T cells in responding patients characterized by higher expression of genes associated with activation, cytotoxicity, and tissue-resident memory markers. Furthermore, compared with CD57 − CD8 T cells, TCRs of CD57 + CD8 T cells showed increased overlap with the TCR repertoire of tumor-infiltrating T cells. Conclusions Collectively, we show high frequencies of CD57 among neoantigen-specific and bulk CD8 T cells in patients responding to atezolizumab. The TCR repertoire overlap between peripheral CD57 + CD8 T cells and tumor-infiltrating lymphocytes suggest that accumulation of peripheral CD57 + CD8 T cells is reflective of an ongoing antitumor T-cell response. Our findings provide evidence and rationale for using circulating CD8 T cells expressing CD57 as a readily accessible blood-based biomarker for selecting patients with mUC for atezolizumab therapy.
Caution Regarding Assessment of Toxic Effects and Survival in Treatment De-escalation With Radiotherapy vs Transoral Surgery for Human Papillomavirus–Associated Oropharyngeal Cancer
Authors: Armando De Virgilio, Andrea Costantino, Giuseppe Spriano
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2022 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Incidence of COVID-19 Among Persons Experiencing Homelessness in the US From January 2020 to November 2021
Authors: Ashley A. Meehan, Isabel Thomas, Libby Horter, Megan Schoonveld, Andrea E. Carmichael, Mitra Kashani, Diana Valencia, Emily Mosites
Journal: JAMA Network Open (2022)

A lack of timely and high-quality data is an ongoing challenge for public health responses to COVID-19 among people experiencing homelessness (PEH). Little is known about the total number of cases of COVID-19 among PEH.To estimate the number of COVID-19 cases among PEH and compare the incidence rate among PEH with that in the general population.This cross-sectional study used data from a survey distributed by the Centers for Disease Control and Prevention to all US state, district, and territorial health departments that requested aggregated COVID-19 data among PEH from January 1, 2020, to September 30, 2021. Jurisdictions were encouraged to share the survey with local health departments.The primary study outcome was the number of cases of COVID-19 identified among PEH. COVID-19 cases and incidence rates among PEH were compared with those in the general population in the same geographic areas.Participants included a population-based sample of all 64 US jurisdictional health departments. Overall, 25 states, districts, and territories completed the survey, among which 18 states (72.0%) and 27 localities reported COVID-19 data among PEH. A total of 26 349 cases of COVID-19 among PEH were reported at the state level and 20 487 at the local level. The annual incidence rate of COVID-19 among PEH at the state level was 567.9 per 10 000 person-years (95% CI, 560.5-575.4 per 10 000 person-years) compared with 715.0 per 10 000 person-years (95% CI, 714.5-715.5 per 10 000 person-years) in the general population. At the local level, the incidence rate of COVID-19 among PEH was 799.2 per 10 000 person-years (95% CI, 765.5-834.0 per 10 000 person-years) vs 812.5 per 10 000 person-years (95% CI, 810.7-814.3 per 10 000 person-years) in the general population.These results provide an estimate of COVID-19 incidence rates among PEH in multiple US jurisdictions; however, a national estimate and the extent of under- or overestimation remain unknown. The findings suggest that opportunities exist for incorporating housing and homelessness status in infectious disease reporting to inform public health decision-making.
COVID-19 infection and its impact on case fatality in patients with pulmonary embolism
Authors: Lukas Hobohm, Ingo Sagoschen, Stefano Barco, Ioannis T. Farmakis, Ugo Fedeli, Sebastian Koelmel, Tommaso Gori, Christine Espinola-Klein, Thomas Münzel, Stavros Konstantinides, Karsten Keller
Journal: European Respiratory Journal (2022)

Background Although a high prevalence of pulmonary embolism (PE) has been reported in association with coronavirus disease 2019 (COVID-19) in critically ill patients, nationwide data on the outcome of hospitalised patients with COVID-19 and PE are still limited. Thus, we investigated seasonal trends and predictors of in-hospital death in patients with COVID-19 and PE in Germany. Methods We used a German nationwide inpatient sample to analyse data on hospitalisations among COVID-19 patients with and without PE during 2020, and to detect changes in PE prevalence and case fatality in comparison with 2019. Results We analysed 176 137 COVID-19 hospitalisations in 2020; PE was recorded in 1.9% (n=3362) of discharge certificates. Almost one-third of patients with COVID-19 and PE died during the in-hospital course (28.7%) compared with COVID-19 patients without PE (17.7%). Between 2019 and 2020, numbers of PE-related hospitalisations were largely unchanged (98 485 versus 97 718), whereas the case fatality rate of PE increased slightly in 2020 (from 12.7% to 13.1%; p&lt;0.001). Differences in case fatality were found between PE patients with and without COVID-19 in 2020 (28.7% versus 12.5%; p&lt;0.001), corresponding to a 3.1-fold increased risk of PE-related death (OR 3.16, 95% CI 2.91–3.42; p&lt;0.001) in the presence of COVID-19. Conclusions In Germany, the prevalence of PE events during hospitalisations was similar in 2019 and 2020. However, the fatality rate among patients with both COVID-19 and PE was substantially higher than that in those with only one of these diseases, suggesting a life-threatening additive prognostic impact of the COVID-19–PE combination.
Caution Regarding Assessment of Toxic Effects and Survival in Treatment De-escalation With Radiotherapy vs Transoral Surgery for Human Papillomavirus–Associated Oropharyngeal Cancer—Reply
Authors: David A. Palma, Anthony C. Nichols
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Postmarketing Colitis Cases Associated With Alpelisib Use Reported to the US Food and Drug Administration
Authors: Kathleen M. Sullivan, Graça M. Dores, Afrouz Nayernama, Tatiana M. Prowell, Shan M. Pradhan, Christy Osgood, S. Christopher Jones
Journal: JAMA Oncology (2022)

This case series investigates reports of 20 patients with colitis temporally associated with alpelisib use.
Physiotherapy. Theory and Clinical Application.
Journal: JAMA (1926)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Comparative Physiology.
Journal: JAMA (1926)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Landscape of pathogenic germline variants in patients with lung cancer.
Authors: Steven Sorscher, Jaclyn LoPiccolo, Elaine Chen, Brandie Heald, Scott T. Michalski, Sarah M. Nielsen, Robert Luke Nussbaum, Renato G. Martins, Edward D. Esplin
Journal: Journal of Clinical Oncology (2022)

388570 Background: Few studies have aimed to investigate the prevalence and spectrum of pathogenic germline variants (PGVs) in patients diagnosed with lung cancer. Given the growing opportunities for precision therapies based on PGVs in DNA damage-repair (DDR)/homologous recombination-repair (HRR) genes and the importance of identifying PGVs to inform future cancer screening and cascade testing, we investigated the prevalence and potential clinical implications of PGVs in individuals with lung cancer. Methods: Deidentified data were retrospectively reviewed for 7,788 individuals diagnosed with lung cancer for whom germline DNA sequencing and exon-level copy number analysis were performed between 2014-2022 at a commercial diagnostic laboratory. The diagnosis of lung cancer was based on ICD-10 codes or language on the test requisition suggesting a primary lung cancer diagnosis. Individuals with requisitions suggesting lung metastases, neuroendocrine tumors or sarcomas as the basis for testing were excluded. Number of genes tested varied per ordering clinician preference. Clinically actionable PGVs were defined as those associated with clinical management recommendations or trial eligibility per current, standard of care guidelines. Descriptive statistics were utilized. Results: The cohort was predominantly female (71.1%), White (64.5%), and most had a history of &gt; 1 cancer (71.1%). A median of 79 genes (range 1-159) were tested. Testing identified 1,503 PGVs in 81 known cancer-risk genes in 1,161/7,788 (14.9%) patients; an additional 229 (2.9%) patients carried a single PGV in a gene associated with autosomal recessive inheritance. PGV rates stratified by self-reported ancestry: Black/African American, 11.8%; Asian or Pacific Islander, 11.8%; Hispanic, 14.5%; White, 15.4%. Among genes with &gt;1,000 individuals tested, PGVs were most common in BRCA2 (2.8%), CHEK2 (2.1%), ATM (1.9%), TP53 (1.3%), BRCA1 (1.2%), and EGFR (1.0%). Of 1,161 individuals, 712 (61.3%) had a PGV in a DDR/HRR gene, making them potentially eligible for a clinical treatment trial, and 1,104/1,161 (95.1%) had a PGV that was potentially clinically actionable. Conclusions: From this large cohort of individuals with lung cancer, 14.9% had PGVs, nearly all of which were clinically actionable. Notably, HRR PGVs were common (64%). Currently, the U.S. Food and Drug Administration has approved and the National Comprehensive Cancer Network Guidelines endorse targeted therapies for patients with breast, pancreatic, prostate, and ovarian cancers who carry HRR PGVs. Recently, the NCCN Guidelines panel recommended germline testing be considered for all patients diagnosed with colorectal cancer. Given the profound implications for both patients and their families that result from identifying PGVs, our results suggest that all patients with lung cancer also be considered for germline genetic testing.
Programmable antivirals targeting critical conserved viral RNA secondary structures from influenza A virus and SARS-CoV-2
Authors: Rachel J. Hagey, Menashe Elazar, Edward A. Pham, Siqi Tian, Lily Ben-Avi, Claire Bernardin-Souibgui, Matthew F. Yee, Fernando R. Moreira, Meirav Vilan Rabinovitch, Rita M. Meganck, Benjamin Fram, Aimee Beck, Scott A. Gibson, Grace Lam, Josephine Devera, Wipapat Kladwang, Khanh Nguyen, Anming Xiong, Steven Schaffert, Talia Avisar, Ping Liu, Arjun Rustagi, Carl J. Fichtenbaum, Phillip S. Pang, Purvesh Khatri, Chien-Te Tseng, Jeffery K. Taubenberger, Catherine A. Blish, Brett L. Hurst, Timothy P. Sheahan, Rhiju Das, Jeffrey S. Glenn
Journal: Nature Medicine (2022)
Cancer-associated fibroblasts employ NUFIP1-dependent autophagy to secrete nucleosides and support pancreatic tumor growth
Authors: Meng Yuan, Bo Tu, Hengchao Li, Huanhuan Pang, Nan Zhang, Minghe Fan, Jingru Bai, Wei Wang, Zhaoqi Shu, Christopher C. DuFort, Sihan Huo, Jie Zhai, Ke Yao, Lina Wang, Haoqiang Ying, Wei-Guo Zhu, Deliang Fu, Zeping Hu, Ying Zhao
Journal: Nature Cancer (2022)
Single-cell analysis and functional characterization uncover the stem cell hierarchies and developmental origins of rhabdomyosarcoma
Authors: Yun Wei, Qian Qin, Chuan Yan, Madeline N. Hayes, Sara P. Garcia, Haibin Xi, Daniel Do, Alexander H. Jin, Tiffany C. Eng, Karin M. McCarthy, Abhinav Adhikari, Maristela L. Onozato, Dimitrios Spentzos, Gunnlaugur P. Neilsen, A. John Iafrate, Leonard H. Wexler, April D. Pyle, Mario L. Suvà, Filemon Dela Cruz, Luca Pinello, David M. Langenau
Journal: Nature Cancer (2022)
Neoadjuvant Chemotherapy, Excision, and Observation for Early Rectal Cancer: The Phase II NEO Trial (CCTG CO.28) Primary End Point Results
Authors: Hagen F. Kennecke, Chris J. O'Callaghan, Jonathan M. Loree, Hussein Moloo, Rebecca Auer, Derek J. Jonker, Manoj Raval, Reilly Musselman, Grace Ma, Antonio Caycedo-Marulanda, Vlad V. Simianu, Sunil Patel, Lacey D. Pitre, Ramzi Helewa, Vallerie L. Gordon, Katerina Neumann, Halla Nimeiri, Max Sherry, Dongsheng Tu, Carl J. Brown
Journal: Journal of Clinical Oncology (2022)

Organ-sparing therapy for early-stage I/IIA rectal cancer is intended to avoid functional disturbances or a permanent ostomy associated with total mesorectal excision (TME). The objective of this phase II trial was to determine the outcomes and organ-sparing rate of patients with early-stage rectal cancer treated with neoadjuvant chemotherapy followed by transanal excision surgery (TES).This phase II trial included patients with clinical T1-T3abN0 low- or mid-rectal adenocarcinoma eligible for endoscopic resection who were treated with 3 months of chemotherapy (modified folinic acid-fluorouracil-oxaliplatin 6 or capecitabine-oxaliplatin). Those with evidence of response proceeded to transanal endoscopic surgery 2-6 weeks later. The primary end point was protocol-specified organ preservation rate, defined as the proportion of patients with tumor downstaging to ypT0/T1N0/X and who avoided radical surgery.Of 58 patients enrolled, all commenced chemotherapy and 56 proceeded to surgery. A total of 33/58 patients had tumor downstaging to ypT0/1N0/X on the surgery specimen, resulting in an intention-to-treat protocol-specified organ preservation rate of 57% (90% CI, 45 to 68). Of 23 remaining patients recommended for TME surgery on the basis of protocol requirements, 13 declined and elected to proceed directly to observation resulting in 79% (90% CI, 69 to 88) achieving organ preservation. The remaining 10/23 patients proceeded to recommended TME of whom seven had no histopathologic residual disease. The 1-year and 2-year locoregional relapse-free survival was, respectively, 98% (95% CI, 86 to 100) and 90% (95% CI, 58 to 98), and there were no distant recurrences or deaths. Minimal change in quality of life and rectal function scores was observed.Three months of induction chemotherapy may successfully downstage a significant proportion of patients with early-stage rectal cancer, allowing well-tolerated organ-preserving surgery.